In spite of intensive investigations in many laboratories, both the etiology and pathogenetic mechanisms leading to multiple sclerosis (MS) remain unsolved. Among several unexplained immunological observations has been the observation that circulating immune complexes have been noted in these patients and that elevated levels of circulating complexes are noted in the CSF of these patients during acute exacerbations of the disease. However, neither the nature of the antigen(s) nor their role in the disease process is known. Encouraged by prior success in detecting antigens within circulating complexes, studies are underway of possible antigen(s) within MS immune complexes which have been quantitated and injected into rabbits. The rabbit anti immune complex sera were tested by either crossed immunoelectrophoresis (CIE) or immunoblotting procedures against brain extracts solubilized from either MS or non MS autopsy brain material. Our results indicate that MS immune complexes do contain brain antigens which are present in both MS and non MS brain. In addition, these antigens appear to be cross reactive with certain components of measles virus. While autoantibodies have already been identified in MS, it is hoped that the association with a viral antigen will identify which brain antigen is responsible for the inciting event in this disease. The goal is now to further identify and purify the brain antigen(s) using both the CIE and ELISA techniques as well as affinity studies and to determine which measles viral antigen is cross reactive with the brain antigen(s). Antibodies in both serum and CSF samples of MS patients will be assayed for reactivity directed towards brain antigens similar to those found in the complexes and whether they fluctuate during disease periods. Monoclonal antibodies will be raised to the pertinent brain antigens. Finally, previous evidence suggests that the events leading to MS occur in the genetically susceptible host. An attempt will be made to identify a unique B cell marker apart from the HLA system with more specificity for multiple sclerosis.